title: Ent-16β,17-dihydroxy-kauran-19-oic acid, a kaurane diterpene acid from Siegesbeckia pubescens, presents antiplatelet and antithrombotic effects in rats.
abstract: The antiplatelet and antithrombotic effects of ent-16β,17-dihydroxy-kauran-19-oic acid (DDKA) isolated from Siegesbeckia pubescens were investigated with different methods both in vitro and in vivo. We tested the antithrombotic activity of DDKA in arterio-venous shunt model. The effects of DDKA on adenosine diphosphate (ADP)-, Thrombin-, Arachidonic acid-induced rat platelets aggregation were tested in vitro. We also assessed its bleeding side effect by measuring coagulation parameters after intravenous administration for 5 days and investigated the potential mechanisms underlying such activities. In vivo, DDKA significantly reduced thrombus weight in the model of arterio-venous shunt. Meanwhile, DDKA increased plasma cAMP level determined by radioimmunoassay in the same model. Notably, DDKA prolonged PT and APTT in rats after intravenous administration DDKA for successive 5 days. In vitro, pretreatment with DDKA on washed rat platelets significantly inhibited various agonists stimulated platelet aggregation and caused an increase in cAMP level in platelets activated by ADP. These findings support our hypothesis that DDKA possesses antiplatelet and antithrombotic activities. The mechanisms underlying such activities may involve the anticoagulatory effect and cAMP induction.
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, College of Pharmacy, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China.
authors.forename: J P
authors.initials: JP
authors.lastname: Wang
authors.forename: H X
authors.initials: HX
authors.lastname: Xu
authors.forename: Y X
authors.initials: YX
authors.lastname: Wu
authors.forename: Y J
authors.initials: YJ
authors.lastname: Ye
authors.forename: J L
authors.initials: JL
authors.lastname: Ruan
authors.forename: C M
authors.initials: CM
authors.lastname: Xiong
authors.forename: Y L
authors.initials: YL
authors.lastname: Cai
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D003328:Coronary Thrombosis / Q000188:drug therapy; D000242:Cyclic AMP / Q000097:blood; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000494:pharmacology*; D011464:Epoprostenol / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood; D013954:Thyroglobulin / Q000097:blood
chemical_list: C058051:6-ketoprostaglandin F1 alpha-thyroglobulin conjugate; D045786:Diterpenes, Kaurane; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C518478:ent-16alphaH,17-hydroxy-kauran-19-oic acid; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D013954:Thyroglobulin; D011464:Epoprostenol; D000242:Cyclic AMP; D013917:Thrombin